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Aliases for MAP3K8 Gene

Aliases for MAP3K8 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase 8 2 3
  • Tumor Progression Locus 2 3 4
  • Proto-Oncogene C-Cot 3 4
  • Tpl-2 3 4
  • ESTF 3 4
  • COT 3 4
  • Proto-Oncogene Serine/Threoine Protein Kinase 3
  • Augmented In Rheumatoid Arthritis 2 3
  • Cot (Cancer Osaka Thyroid) Oncogene 3
  • Serine/Threonine-Protein Kinase Cot 4
  • Cancer Osaka Thyroid Oncogene 4
  • Ewing Sarcoma Transformant 3
  • EC 2.7.11.25 4
  • AURA2 3
  • MEKK8 3
  • C-COT 3
  • TPL2 3
  • EST 3

External Ids for MAP3K8 Gene

Previous HGNC Symbols for MAP3K8 Gene

  • COT
  • ESTF

Previous GeneCards Identifiers for MAP3K8 Gene

  • GC10P030873
  • GC10P030726
  • GC10P030762
  • GC10P030722

Summaries for MAP3K8 Gene

Entrez Gene Summary for MAP3K8 Gene

  • This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]

GeneCards Summary for MAP3K8 Gene

MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8) is a Protein Coding gene. Diseases associated with MAP3K8 include lung cancer. Among its related pathways are MAPK signaling pathway and Immune System. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is MAP3K5.

UniProtKB/Swiss-Prot for MAP3K8 Gene

  • Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.

Gene Wiki entry for MAP3K8 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MAP3K8 Gene

Genomics for MAP3K8 Gene

Regulatory Elements for MAP3K8 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for MAP3K8 Gene

Chromosome:
10
Start:
30,433,937 bp from pter
End:
30,461,833 bp from pter
Size:
27,897 bases
Orientation:
Plus strand

Genomic View for MAP3K8 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for MAP3K8 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP3K8 Gene

Proteins for MAP3K8 Gene

  • Protein details for MAP3K8 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P41279-M3K8_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase 8
    Protein Accession:
    P41279
    Secondary Accessions:
    • A8K2Q5
    • D3DRX1
    • Q14275
    • Q5T855
    • Q9HC81

    Protein attributes for MAP3K8 Gene

    Size:
    467 amino acids
    Molecular mass:
    52925 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Forms a ternary complex with NFKB1/p105 and TNIP2. Interacts with NFKB1; the interaction increases the stability of MAP3K8 but inhibits its MEK phosphorylation activity, whereas loss of interaction following LPS stimulation leads to its degradation. Interacts with CD40 and TRAF6; the interaction is required for ERK activation. Interacts with KSR2; the interaction inhibits ERK and NF-kappa-B activation.
    Miscellaneous:
    • Can be converted to an oncogenic protein by proviral activation, leading to a C-terminally truncated protein with transforming activity

    Three dimensional structures from OCA and Proteopedia for MAP3K8 Gene

    Alternative splice isoforms for MAP3K8 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP3K8 Gene

Proteomics data for MAP3K8 Gene at MOPED

Post-translational modifications for MAP3K8 Gene

  • Autophosphorylated. Isoform 1 undergoes phosphorylation mainly on Ser residues, and isoform 2 on both Ser and Thr residues. Thr-290 is autophosphorylated (PubMed:19754427) and/or transphosphorylated (PubMed:15466476); the phosphorylation is necessary but not sufficient for full kinase activity in vitro and for the dissociation of isoform 1 from NFKB1, leading to its degradation. Ser-400 is autophosphorylated (PubMed:19754427) and/or transphosphorylated by IKBKB (PubMed:22988300); the phosphorylation is required for LPS-stimulated activation of the MAPK/ERK pathway in macrophages.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MAP3K8 Gene

Antibody Products

  • R&D Systems Antibodies for MAP3K8 (MAP3K8/Tpl2/COT)
  • Cell Signaling Technology (CST) Antibodies for MAP3K8 (Cot)

No data available for DME Specific Peptides for MAP3K8 Gene

Domains & Families for MAP3K8 Gene

Protein Domains for MAP3K8 Gene

Graphical View of Domain Structure for InterPro Entry

P41279

UniProtKB/Swiss-Prot:

M3K8_HUMAN :
  • Contains 1 protein kinase domain.
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Domain:
  • Contains 1 protein kinase domain.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
genes like me logo Genes that share domains with MAP3K8: view

Function for MAP3K8 Gene

Molecular function for MAP3K8 Gene

GENATLAS Biochemistry:
mitogen-activated protein kinase kinase kinase 8,with two alternatively spliced transcripts
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot Function:
Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.
UniProtKB/Swiss-Prot Induction:
Up-regulated by IL12 in T-lymphocytes. Up-regulated in subcutaneous adipose tissue of obese individuals.

Enzyme Numbers (IUBMB) for MAP3K8 Gene

Gene Ontology (GO) - Molecular Function for MAP3K8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IEA --
GO:0004672 protein kinase activity --
GO:0004674 protein serine/threonine kinase activity TAS 8226782
GO:0004709 MAP kinase kinase kinase activity IEA --
GO:0005515 protein binding IPI 12832462
genes like me logo Genes that share ontologies with MAP3K8: view
genes like me logo Genes that share phenotypes with MAP3K8: view

Animal Models for MAP3K8 Gene

MGI Knock Outs for MAP3K8:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for MAP3K8

In Situ Assay Products

Flow Cytometry Products

No data available for Transcription Factor Targets and HOMER Transcription for MAP3K8 Gene

Localization for MAP3K8 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP3K8 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MAP3K8 Gene COMPARTMENTS Subcellular localization image for MAP3K8 gene
Compartment Confidence
cytosol 4
nucleus 2
extracellular 1

Gene Ontology (GO) - Cellular Components for MAP3K8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular --
GO:0005737 cytoplasm IDA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with MAP3K8: view

Pathways & Interactions for MAP3K8 Gene

genes like me logo Genes that share pathways with MAP3K8: view

SIGNOR curated interactions for MAP3K8 Gene

Activates:
Is inactivated by:

Gene Ontology (GO) - Biological Process for MAP3K8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade --
GO:0000186 activation of MAPKK activity IEA --
GO:0002224 toll-like receptor signaling pathway TAS --
GO:0002755 MyD88-dependent toll-like receptor signaling pathway TAS --
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with MAP3K8: view

Drugs & Compounds for MAP3K8 Gene

(5) Drugs for MAP3K8 Gene - From: HMDB, DGIdb, and NovoSeek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
MEK INHIBITOR II Pharma 0
TPL2 KINASE INHIBITOR Pharma 0
Magnesium Nutra 0
serine Nutra 420
threonine Nutra 16
genes like me logo Genes that share compounds with MAP3K8: view

Transcripts for MAP3K8 Gene

Unigene Clusters for MAP3K8 Gene

Mitogen-activated protein kinase kinase kinase 8:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for MAP3K8

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for MAP3K8 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3a · 3b · 3c ^ 4a · 4b · 4c · 4d ^ 5 ^ 6a · 6b · 6c ^ 7 ^ 8 ^ 9 ^ 10
SP1: - - - - -
SP2:
SP3: - - - - - -
SP4: - - - -
SP5: - - -
SP6: - - -
SP7: - -

Relevant External Links for MAP3K8 Gene

GeneLoc Exon Structure for
MAP3K8
ECgene alternative splicing isoforms for
MAP3K8

Expression for MAP3K8 Gene

mRNA expression in normal human tissues for MAP3K8 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MAP3K8 Gene

This gene is overexpressed in Colon muscle (51.6) and Esophagus (11.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for MAP3K8 Gene



SOURCE GeneReport for Unigene cluster for MAP3K8 Gene Hs.432453

mRNA Expression by UniProt/SwissProt for MAP3K8 Gene

P41279-M3K8_HUMAN
Tissue specificity: Expressed in several normal tissues and human tumor-derived cell lines
genes like me logo Genes that share expression patterns with MAP3K8: view

Protein tissue co-expression partners for MAP3K8 Gene

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for MAP3K8 Gene

Orthologs for MAP3K8 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for MAP3K8 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia MAP3K8 35
  • 88.72 (n)
  • 96.36 (a)
MAP3K8 36
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MAP3K8 35
  • 91.51 (n)
  • 97.22 (a)
MAP3K8 36
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Map3k8 35
  • 87.79 (n)
  • 93.36 (a)
Map3k8 16
Map3k8 36
  • 93 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia MAP3K8 35
  • 99.14 (n)
  • 99.57 (a)
MAP3K8 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Map3k8 35
  • 87.65 (n)
  • 94 (a)
oppossum
(Monodelphis domestica)
Mammalia MAP3K8 36
  • 87 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MAP3K8 36
  • 91 (a)
OneToOne
chicken
(Gallus gallus)
Aves MAP3K8 35
  • 76.2 (n)
  • 84.09 (a)
MAP3K8 36
  • 80 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MAP3K8 36
  • 77 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia map3k8 35
  • 69.54 (n)
  • 71.34 (a)
zebrafish
(Danio rerio)
Actinopterygii map3k8 35
  • 62.1 (n)
  • 62.92 (a)
map3k8 36
  • 59 (a)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes BCK1 36
  • 7 (a)
OneToMany
Species with no ortholog for MAP3K8:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for MAP3K8 Gene

ENSEMBL:
Gene Tree for MAP3K8 (if available)
TreeFam:
Gene Tree for MAP3K8 (if available)

Paralogs for MAP3K8 Gene

Paralogs for MAP3K8 Gene

(2) SIMAP similar genes for MAP3K8 Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with MAP3K8: view

Variants for MAP3K8 Gene

Sequence variations from dbSNP and Humsavar for MAP3K8 Gene

SNP ID Clin Chr 10 pos Sequence Context AA Info Type MAF
rs2907 -- 30,439,321(+) TTCCT(A/G)CTGCA intron-variant
rs3034 -- 30,460,966(+) GACCC(A/G)TGAAT utr-variant-3-prime
rs303426 -- 30,451,450(+) TGATG(A/G)ATCCA intron-variant
rs303427 -- 30,450,851(+) CTGTG(A/G)CAAGT intron-variant
rs303428 -- 30,450,129(+) AGTCC(A/G)TTTTC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for MAP3K8 Gene

Variant ID Type Subtype PubMed ID
nsv831821 CNV Loss 17160897
nsv894994 CNV Gain 21882294
nsv831822 CNV Gain 17160897
esv267738 CNV Insertion 20981092

Variation tolerance for MAP3K8 Gene

Residual Variation Intolerance Score: 15.32% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.71; 32.47% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for MAP3K8 Gene

HapMap Linkage Disequilibrium report
MAP3K8
Human Gene Mutation Database (HGMD)
MAP3K8

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP3K8 Gene

Disorders for MAP3K8 Gene

MalaCards: The human disease database

(1) MalaCards diseases for MAP3K8 Gene - From: OMIM

Disorder Aliases PubMed IDs
lung cancer
  • lung cancer, protection against
- elite association

Relevant External Links for MAP3K8

Genetic Association Database (GAD)
MAP3K8
Human Genome Epidemiology (HuGE) Navigator
MAP3K8
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
MAP3K8
genes like me logo Genes that share disorders with MAP3K8: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MAP3K8 Gene

Publications for MAP3K8 Gene

  1. Structure and transforming potential of the human cot oncogene encoding a putative protein kinase. (PMID: 2072910) Miyoshi J. … Kakunaga T. (Mol. Cell. Biol. 1991) 2 23 67
  2. Tpl2 kinase is upregulated in adipose tissue in obesity and may mediate interleukin-1beta and tumor necrosis factor-{alpha} effects on extracellular signal-regulated kinase activation and lipolysis. (PMID: 19808894) Jager J. … Tanti J.F. (Diabetes 2010) 23 67
  3. Inhibition of tumor progression locus 2 protein kinase suppresses receptor activator of nuclear factor-kappaB ligand-induced osteoclastogenesis through down-regulation of the c-Fos and nuclear factor of activated T cells c1 genes. (PMID: 20045951) Hirata K. … Sugiyama E. (Biol. Pharm. Bull. 2010) 23 67
  4. Tpl-2 kinase downregulates the activity of p53 and enhances signaling pathways leading to activation of activator protein 1 induced by EGF. (PMID: 19221002) Khanal P. … Choi H.S. (Carcinogenesis 2009) 23 67
  5. BCL11B enhances TCR/CD28-triggered NF-kappaB activation through up-regulation of Cot kinase gene expression in T-lymphocytes. (PMID: 18831712) Cismasiu V.B. … Avram D. (Biochem. J. 2009) 23 67

Products for MAP3K8 Gene

Sources for MAP3K8 Gene

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